Thermophilic adaptation of proteins

Hyperthermophilic organisms optimally grow dose to the boiling point of wat er. As a consequence, their macromolecules must be much more thermostable t han those from mesophilic species. Here, proteins from hyperthermophiles an d mesophiles are compared with respect to their thermodynamic and kinetic s tabilities. The known differences in amino acid sequences and three-dimensi onal structures between intrinsically thermostable and thermolabile protein s will be summarized, and the crucial role of electrostatic interactions fo r protein stability at high temperatures will be highlighted. Successful at tempts to increase the thermostability of proteins, which were either based on rational design or on directed evolution, are presented. The relationsh ip between high thermo-stability of enzymes from hyperthermophiles and thei r low catalytic activity at room temperature is discussed. Not all proteins from hyperthermophiles are thermostable enough to retain their structures and functions at the high physiological temperatures. It will be shown how this shortcoming can be surpassed by extrinsic factors such as large molecu lar chaperones and small compatible solutes. Finally, the potential of ther mostable enzymes for biotechnology is discussed.